Cortical, subcortical, brainstem and autonomic responses to nociception under total intravenous anesthesia

Physiological responses to nociception are complex and involve intricate associations between the central, peripheral, and autonomic nervous systems. To optimize intraoperative analgesic titration, several monitoring devices have been developed, each targeting specific physiologic variables. However, existing devices primarily focus on isolated components of the nociceptive response, such as autonomic or cortical activity, without integrating these perspectives comprehensively. Our aim was to compare the performance of different nociception monitors in response to standardized tetanic stimulation and to investigate the correlation between these monitors' responses and varying concentrations of remifentanil.

In this study, we evaluated and compared the responses of the Nociception Level index (NOL), Analgesia Nociception Index (ANI), Pupillary Reflex Dilation (PRD) and both raw and processed electroencephalogram (EEG) under varying concentrations of propofol and remifentanil. Standardized tetanic stimuli were administered to patients under general anesthesia with target-controlled infusion of propofol and remifentanil. EEG, PRD, NOL, ANI, heart rate (HR), Bispectral index (BIS), and CONOX monitor indices (qCON and qNOX) were concomitantly recorded.

ANI, BIS, HR, NOL, PRD, and qNOX significantly changed after noxious stimulation. In our dataset, PRD had the strongest correlation with varying remifentanil concentrations, while ANI, NOL, and qNOX did not show significant correlations with remifentanil concentrations. Following a noxious stimulus, the raw EEG in patients with low PRD exhibited a significant increase in power in the high EEG frequencies around 25 Hz and decreased power in frequencies corresponding to the alpha range (8-12 Hz) in the power spectral density.

PRD, HR, and BIS correlated with varying levels of remifentanil, with PRD exhibiting the strongest correlation. When CE remifentanil are low, noxious stimuli are more likely to dilate the pupil and be detected in the EEG. Considering the complexity of the nociceptive response, integrating multimodal neurophysiologic monitoring with pharmacological data may improve the anesthesiologist's ability to assess on the nociception-antinociception balance. However, further studies are needed to validate these findings and address the study's limitations.